GPCRs I Flashcards
What is the largest family of cell surface receptors and important drug target?
GPCRs
How many human GPCRs are there
800
Rough GCPR signalling pathway
Activated GPCR binds heterotrimeric G proteins and promotes exchanged of GDP for GTP in the alpha subunit. This causes alpha to dissociate from beta and gamma.
What activates effector proteins?
The GTP bound alpha subunit and beta-gamma dimer
Three important second messengers
cAMP, IP3 (inositol triphosphate) and Ca2+
Adenylyl cyclase pathway
Adenylyl cyclase produces cAMP, which activates PKA, which phosphorylates effector proteins such as ion channels or transcription factors
What does high serotonin levels cause?
High cAMP, activates PKA channels, inhibits K+ channels
Adenylyl cyclase structure
12 TM helices, main catalytic domain in cytosolic region, dimer
PLC-beta function
Cleaves PIP2 (phosphatidylinositol 4,5-bisphosphate) to produce IP3 (inositol 1,4,5-triphosphate) and diacylglycerol. IP3 opens Ca2+ channels in the ER. DAG activates PKC
PLC-beta structure
Associated with the membrane and cleaves lipids with inositol attached
IP3 and ryanodine receptors
Receptor opens, Ca2+ flows out, Ca2+ activates receptors nearby (+ve feedback), Ca2+ too high = inhibition (-ve feedback). Pulsating wave of Ca2+
Ca2+ in egg cell
Wave of Ca2+ changes surface of egg cell to prevent entry of other sperm
Vasopressin-induced Ca2+ oscillations in liver cells
Informs liver cells to breakdown glycogen
What happens when there’s an increase in cytosolic Ca2+?
Leads to calmodulin dependent activation of CAMKII and other effector proteins
How many calciums bind to calmodulin and what happens
4 calciums bind and it causes calmodulin to rigidify and the central helix forms properly
